Studies have continued on the mechanism by which specific pathogenic bacteria evade killing by the serum complement system. Studies comparing serum resistant and serum sensitive strains of Neisseria gonorrhoeae showed equivalent binding of the complement membrane attack complex (C5b-9) to the surface of these organisms. Presensitization of resistant GC with bactericidal rabbit IgG resulted in killing by serum, but killing could not be explained simply by increasing terminal complement component deposition of the bacterial surface. Sucrose density gradient ultracentrifugation of detergent extracted C5b-9 complexes indicated that the complex on sensitive organism sedimented as a major sharp 33s peak whereas the complex from the resistant strains contained broad peaks of 35s and 43s. C5b-9 co-precipitated with outer membrane constituents of sensitive and resistant GC in double diffusion and quantitative immunoprecipitation reactions. We concluded that the C5b-9 complex is in a different molecular configuration on the surface of the resistant organism than on the surface of the sensitive isolate or the resistant strain rendered sensitive with antibody. In studies with E. coli 0111B4 we found that bactericidal antibody is required for killing in serum, but that antibody increases primarily the bactericidal efficiency rather the number of C5b-9 deposited on the bacterial membrane. Antibody must be present at or before C5 convertase formation to cause killing. This conclusion was based on the finding that presensitized bacteria were killed in dose-related fashion as serum concentration was raised, compared with minimal killing of non-presensitized organisms at all serum concentrations. However, binding of C3 and C9 on presensitized bacteria was not significantly different from binding on non-presensitized organisms. Antibody dependent killing was mediated via the alternative pathway by IgG and F(ab')2 but not F(ab').